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Method: Quantifying pathological progression from single-cell transcriptomic data with scPSS
- Samin Rahman Khan,
- M Saifur Rahman,
- M. Sohel Rahman,
- and Md Abul Hassan Samee
Genome Res. February 2026 36: 375-386; Published in Advance January 14, 2026, doi:10.1101/gr.280411.125
...be used to predict health conditions at the individual level.The ability to measure cellular state transitions between healthy and diseased conditions is fundamental to understanding disease mechanisms and progression. The increasing availability of single-cell data sets and large-scale reference atlases...
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Method: Recovering gene regulatory networks in single-cell multi-omics data with PRISM-GRN
- Wenhao Zhang,
- Lan Cao,
- Xiaoxuan Gu,
- Yongyu Long,
- and Ying Wang
Genome Res. January 2026 36: 142-158; Published in Advance October 9, 2025, doi:10.1101/gr.280757.125
...and target genes (Gao et al. 2023).Single-cell RNA sequencing (scRNA-seq) enables gene expression profiling at the individual cell level, revealing cellular heterogeneity with single-cell resolution and significantly enhancing the understanding of cell type–specific gene regulation (Chen and Liu 2022; Kartha...
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Method: De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data
- Arthur Dondi,
- Nico Borgsmüller,
- Pedro F. Ferreira,
- Brian J. Haas,
- Francis Jacob,
- Viola Heinzelmann-Schwarz,
- Tumor Profiler Consortium,
- and Niko Beerenwinkel
Genome Res. April 2025 35: 900-913; Published in Advance March 19, 2025, doi:10.1101/gr.279281.124
....beerenwinkel@bsse.ethz.chAbstractIn cancer, genetic and transcriptomic variations generate clonal heterogeneity, leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential to detect genetic and transcriptomic variations simultaneously. Here, we present LongSom, a computational workflow leveraging...
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Method: Inferring disease progression stages in single-cell transcriptomics using a weakly supervised deep learning approach
- Fabien Wehbe,
- Levi Adams,
- Jordan Babadoudou,
- Samantha Yuen,
- Yoon-Seong Kim,
- and Yoshiaki Tanaka
Genome Res. January 2025 35: 135-146; Published in Advance December 2, 2024, doi:10.1101/gr.278812.123
...is applicable across multiple independent single-cell RNA sequencing (scRNA-seq) data sets. Using the pretrained model of the PD scRNA-seq data set (midbrains of young and aged healthy donors and PD patients) (as used in Fig. 1; Adams et al. 2024), we inferred disease progression levels of individual cells...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
...-read single-cell RNA sequencing (scRNA-seq) data reveals significant gene expression differences in SF3B1-mutated CLL cells, although it does not impact the sensitivity of the anticancer drug venetoclax. scRaCH-seq's capability to study long-read transcripts of multiple genes makes it a powerful tool...
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Review: Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics
- Natan Belchikov,
- Justine Hsu,
- Xiang Jennie Li,
- Julien Jarroux,
- Wen Hu,
- Anoushka Joglekar,
- and Hagen U. Tilgner
Genome Res. November 2024 34: 1735-1746; doi:10.1101/gr.279640.124
..., at the time of writing, single-cell short-read RNA sequencing is a widely employed technology that has significantly contributed to our understanding of physiology and disease in human, mouse, and other model organisms (Fig. 2A). Many consortium-led research programs now seek to comprehensively catalog...
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Review: Advancements in prospective single-cell lineage barcoding and their applications in research
- Xiaoli Zhang,
- Yirui Huang,
- Yajing Yang,
- Qi-En Wang,
- and Lang Li
Genome Res. December 2024 34: 2147-2162; Published in Advance November 21, 2024, doi:10.1101/gr.278944.124
...of misidentifying the correct cell groups. These inaccuracies introduce biases into the depiction of the complexity of biological processes, impeding an accurate understanding of the molecular mechanisms involved (Kester and van Oudenaarden 2018).The recent breakthrough in single-cell RNA sequencing (scRNA-seq) has...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...short-read sequences. Recent advances in long-read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single-cell samples. Here, we developed a new computational tool, CTAT-LR-Fusion, to detect fusion transcripts from long-read RNA-seq with or without...
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Method: Polyomino reconstructs spatial transcriptomic profiles with single-cell resolution via a region-allocation method
- Quanyou Cai,
- Lihui Lin,
- Xin Liu,
- and Jiekai Chen
Genome Res. November 2025 35: 2513-2526; Published in Advance October 22, 2025, doi:10.1101/gr.280532.125
.... The Polyomino algorithm converged after 500 epochs with default parameters.Mapping single-cell data to Visium dataWe used processed data of colorectal cancer–derived liver metastatic tumor (Wang et al. 2023) from the BD Rhapsody Single-Cell Whole Transcriptome platform, sequencing a total of 115,818 cells...
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Research: Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotypes and phenotypes in chronic lymphocytic leukemia
- Gage S. Black,
- Xiaomeng Huang,
- Yi Qiao,
- Philip Moos,
- Deepa Sampath,
- Deborah M. Stephens,
- Jennifer A. Woyach,
- and Gabor T. Marth
Genome Res. April 2025 35: 686-697; Published in Advance February 18, 2025, doi:10.1101/gr.279049.124
...-mutated subclones exhibit distinct transcriptomic behavior when compared to other cancer subclones. To achieve these goals, we use scBayes, which integrates bulk DNA sequencing and single-cell RNA sequencing (scRNA-seq) data to genotype individual cells for subclone-defining mutations. Although the most common...

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